7-108414791-A-T

Variant names:

• chr7-108414791-A-T
• rs1990162
• NM_001037132.4:c.-331-15198T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001037132.4(NRCAM):​c.-331-15198T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 151,904 control chromosomes in the GnomAD database, including 8,386 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.32 (8386 hom., cov: 31)
• Consequence: NRCAM NM_001037132.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.154
• Publications: 2 publications found

Genes affected

NRCAM (HGNC:7994): (neuronal cell adhesion molecule) Cell adhesion molecules (CAMs) are members of the immunoglobulin superfamily. This gene encodes a neuronal cell adhesion molecule with multiple immunoglobulin-like C2-type domains and fibronectin type-III domains. This ankyrin-binding protein is involved in neuron-neuron adhesion and promotes directional signaling during axonal cone growth. This gene is also expressed in non-neural tissues and may play a general role in cell-cell communication via signaling from its intracellular domain to the actin cytoskeleton during directional cell migration. Allelic variants of this gene have been associated with autism and addiction vulnerability. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

NRCAM Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with neuromuscular and skeletal abnormalities

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.485 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRCAM	NM_001037132.4	c.-331-15198T>A		intron_variant	Intron 1 of 32	ENST00000379028.8	NP_001032209.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRCAM	ENST00000379028.8	c.-331-15198T>A		intron_variant	Intron 1 of 32	5	NM_001037132.4	ENSP00000368314.3

Frequencies

GnomAD3 genomes AF: 0.322 AC: 48896 AN: 151786 Hom.: 8383 Cov.: 31

Gnomad AFR AF: 0.192

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.398

Gnomad ASJ AF: 0.449

Gnomad EAS AF: 0.501

Gnomad SAS AF: 0.439

Gnomad FIN AF: 0.333

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.353

Gnomad OTH AF: 0.360

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.322 AC: 48911 AN: 151904 Hom.: 8386 Cov.: 31 AF XY: 0.327 AC XY: 24246 AN XY: 74248

African (AFR) AF: 0.192 AC: 7941 AN: 41464

American (AMR) AF: 0.397 AC: 6061 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.449 AC: 1554 AN: 3464

East Asian (EAS) AF: 0.501 AC: 2573 AN: 5132

South Asian (SAS) AF: 0.439 AC: 2106 AN: 4794

European-Finnish (FIN) AF: 0.333 AC: 3521 AN: 10566

Middle Eastern (MID) AF: 0.463 AC: 136 AN: 294

European-Non Finnish (NFE) AF: 0.353 AC: 23996 AN: 67914

Other (OTH) AF: 0.368 AC: 774 AN: 2102

Alfa AF: 0.328 Hom.: 1063

Bravo AF: 0.323

Asia WGS AF: 0.491 AC: 1708 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.56
PhyloP100		0.15
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1990162; hg19: chr7-108055235;